Abstract

Ionizing radiation and other oxidative stresses modify the bases in DNA. Several of these bases are substrates for DNA repair enzymes which is evidence that they are also modified by endogenous oxidants. This proposal continues to study formation of derivatives of thymine and cytosine in DNA exposed to oxidative stress. The potential mutagenicity of these modified bases will be studied. A repair enzyme, 5-hydroxymethyluracil-N- glycosylase will be purified so that its genetic expression may be studied. 32P-post labelling techniques for identification of these bases in vivo will be developed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA016669-14
Application #
3481747
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1978-08-01
Project End
1993-03-31
Budget Start
1989-04-12
Budget End
1990-03-31
Support Year
14
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012

  Publications

Ocampo, Maria T A; Chaung, Wenren; Marenstein, Dina R et al. (2002) Targeted deletion of mNth1 reveals a novel DNA repair enzyme activity. Mol Cell Biol 22:6111-21
Boorstein, R J; Cummings Jr, A; Marenstein, D R et al. (2001) Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase activity as SMUG1. J Biol Chem 276:41991-7
Marenstein, D R; Ocampo, M T; Chan, M K et al. (2001) Stimulation of human endonuclease III by Y box-binding protein 1 (DNA-binding protein B). Interaction between a base excision repair enzyme and a transcription factor. J Biol Chem 276:21242-9
Chheda, A D; Teebor, G W; Cunningham, R P (2000) Identification, characterization, and purification of DNA glycosylase/AP lyases by reductive crosslinking to 2'-deoxyribooligonucleotides containing specific base lesions. Methods 22:180-7
Hilbert, T P; Chaung, W; Boorstein, R J et al. (1997) Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III. J Biol Chem 272:6733-40
Hilbert, T P; Boorstein, R J; Kung, H C et al. (1996) Purification of a mammalian homologue of Escherichia coli endonuclease III: identification of a bovine pyrimidine hydrate-thymine glycol DNAse/AP lyase by irreversible cross linking to a thymine glycol-containing oligoxynucleotide. Biochemistry 35:2505-11
Zuo, S; Boorstein, R J; Teebor, G W (1995) Oxidative damage to 5-methylcytosine in DNA. Nucleic Acids Res 23:3239-43
Zuo, S; Boorstein, R J; Cunningham, R P et al. (1995) Comparison of the effects of UV irradiation on 5-methyl-substituted and unsubstituted pyrimidines in alternating pyrimidine-purine sequences in DNA. Biochemistry 34:11582-90
O'Donnell, R E; Boorstein, R J; Cunningham, R P et al. (1994) Effect of pH and temperature on the stability of UV-induced repairable pyrimidine hydrates in DNA. Biochemistry 33:9875-80
Lustig, M J; Cadet, J; Boorstein, R J et al. (1992) Synthesis of the diastereomers of thymidine glycol, determination of concentrations and rates of interconversion of their cis-trans epimers at equilibrium and demonstration of differential alkali lability within DNA. Nucleic Acids Res 20:4839-45

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